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Drug-device combination products should be safe and effective for intended uses by intended users under intended use environment during human factor (HF) studies. All known use errors and use-related problems should be considered during design of device and use-related risk analysis. Availability of such information in a compiled manner is scarce. This review compiles information of use errors reported during HF validation studies of biological combination products (drug + device) approved by USFDA's Centre for Drug Evaluation and Research between 21 June 2011 and 31 December 2019. Information regarding product, indication, type of devices, use errors, root causes and mitigation strategies were collected from published documents. Total 280 use errors were reported during HF validation studies of 39 devices across 5 categories. Overall approach and methodology for use error data collection during HF validation studies was in line with the US FDA recommendations. Performance of participants for critical and essential tasks was evaluated during HF validation studies via simulated use assessment, knowledge task assessment and interview. The root causes for use errors reported during HF validation studies were identified and use errors were mitigated by suitable corrective measures. Instructions for use clarification/improvement and labelling improvement were the most common mitigation strategies implemented across devices.

Regulatory agencies of the USA and European Union (EU) have introduced multiple guidelines in the last decade to standardize and accelerate biosimilar development. As a result, a large number of biosimilars are being approved in the USA and EU. In the present review, we identified the biosimilars and their corresponding reference biologics approved for pediatrics in the USA and EU, and then assessed their approval details. In the USA, a biosimilar applicant needs to submit an initial pediatric study plan under the Pediatric Research Equity Act (PREA). We found that the PREA requirements of a pediatric assessment for biosimilars were waived where the reference biologics were not approved for one or more pediatric age groups for an indication. The PREA requirements of a pediatric assessment were deferred if the indication was under orphan drug exclusivity or a pediatric formulation was not available. Excluding the waiver and deferral scenarios, biosimilars were approved for the same pediatric indications as those of the reference biologics based on scientific justification extrapolation from the pediatric information of the reference biologics to biosimilars. The applicants were asked to submit a pediatric assessment in the deferred indication and/or develop a dedicated formulation that can ensure accurate dose delivery in pediatric population, as applicable. In the EU, pediatric assessments were not required for biosimilars; hence, all biosimilars (except rituximab) have been approved for the same indications as those of the reference biologics. Biosimilar developers need to be aware of the possible requirement of a pediatric study plan, development of pediatric drug delivery devices, and requirement of human factor studies for a device, to avoid delay in approval of biosimilars in the USA.

Introduction : With increasing use of biological products and devices, importance of human factor (HF) studies is increasing. The HF study ensures safe and effective use of the device by intended users, for intended uses, under intended use environments. Areas covered : This review compiles information of HF studies conducted for biological combination products (biological products plus device) approved by US FDA's Center for Drug Evaluation and Research between 21 June 2011 and 31 December 2018. Information regarding product, indication, device type, administration frequency, and various aspects related to HF studies was collected from published documents. Expert opinion : Learnings from HF studies and known use-related problems of similar devices should be incorporated in the design of the device and the HF validation study. User profile, group, subgroup, and sample size are important aspects of the HF validation study. Early engagement with US FDA can be helpful to integrate the HF program with the overall device development program. It may not be possible to eliminate all use errors or risks for the device. Any residual risk after an HF validation study should be evaluated, and benefits of the device use should outweigh the residual risk. Abbreviations : BCP: biological combination product; BLA: Biological License Application; CDER: Center of Drug Evaluation and Research; FDA: Food and Drug Administration; FDC: Food Drug and Cosmetic; HCP: healthcare professional; HF: human factor; IFU: instructions for use; NDA: New Drug Application; PFS: pre-filled syringe; PHS: Public Health Service; PI: prescribing information; US: United States.